Nonsteroidal anti-inflammatory analgesics do not show severe side-effects as shown in steroidal anti-inflammatory analgesics, and thus are drugs widely used in the clinical practice. However, in case where nonsteroidal anti-inflammatory analgesics are orally administered, they show any inhibition activity against cyclooxygenase being a prostaglandin generating enzyme present in the living bodies, and therefore it is recognized to cause side-effects such as stomach mucosa disorder. In order to reduce such side-effects, preparations absorbed through the skin, that is, transdermal preparations are developed.
Bases for the transdermal preparations are classified into two categories, an aqueous base and a nonaqueous base. The nonaqueous base includes a rubbery base, an acrylic base, silicone and the like. In the meantime, when a drug in a salt form is formulated in a nonaqueous base, the application thereof to the skin does not lead to so large amount of skin penetrated drug as to exert the pharmacological effect because compatibility between the drug and the base is low and drug-releasing characteristics from the base is extremely low. Further, as the drug is not dissolved in the base, there is also a problem that the drug availability is low. In practice, the comparative experiments on drug-releasing characteristics and skin penetration between an drug in a salt form added in a nonaqueous base and an drug in no salt form added in a nonaqueous base confirm that the drug in a salt form is low in releasing characteristics and skin penetration compared with the drug in no salt form.
However, many of the prior arts on transdermal preparation containing anti-inflammatory analgesic as an active ingredient do not distinguish between drugs in no salt form and drugs in a salt form as an active ingredient that is contained in the preparation or may be added in the base, and most of the prior arts only state the name of a drug in a salt form as mere example of anti-inflammatory analgesic. For example, it is reported an anti-inflammatory analgesic plaster prepared by applying a base component comprising at least one nonsteroidal anti-inflammatory analgesic selected from ketoprofen, flurbiprofen, loxoprofen, ketorolac, and the ester derivatives and salts thereof, a solvent comprising both a rosin ester derivative and 1-menthol, a styrene-isoprene-styrene block copolymer as a base polymer, and a softener, on a support made of polyester fabric (see, for example Patent Document 1). The anti-inflammatory analgesic plaster accomplishes an improvement in percutaneous absorption and drug-releasing characteristics, reduction of side-effects such as skin irritation or the like, and simple usability by formulating the above-mentioned base components. However, the document do not distinguish as nonsteroidal anti-inflammatory analgesic, drugs in a salt form from drugs in no salt form, and therefore the plaster is clearly unsuitable for the above-mentioned reasons.
On the other hand, it is also known an anti-inflammatory analgesic plaster prepared by laminating a pressure-sensitive adhesive material layer containing a nonsteroidal anti-inflammatory analgesic in an alkali metal salt form and an organic acid that is strongly acidic compared with the nonsteroidal anti-inflammatory analgesic in a free form, on a flexible support (see, for example Patent Document 2). Since, most of the organic acid have alcoholic hydroxy group, the hydroxy group is reacted with carbonyl group of carboxylic acid on the nonsteroidal anti-inflammatory analgesic represented by loxoprofen sodium to give an ester that causes a problem that the stability of the anti-inflammatory analgesic is lowered.
Patent Document 1: JP Patent No. 2816765 (1998)
Patent Document 2: JP B 7-47535 (1995)